The present invention relates to the crystal form II of 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, to a process for preparing this substance and to its use for controlling unwanted midroorganisms.
2-[2-(1-Chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione and its use as microbicide, in particular as fungicide, are already known (cf. WO 96-16 048). It is also known that this substance can be prepared by reacting 2-(1-chlorocyclopropyl)-1-(2-chlorophenyl)-3-(1,2,4-triazol-1-yl)propan-2-ol either (a) with sulphur in the presence of N-methylpyrrolidone at temperatures of about 200° C. or (b) initially with n-butyllithium in the presence of hexane and then with sulphur in the presence of tetrahydrofuran (cf. WO 96-16 048). It has now been found that the active compound can be obtained in two different crystal forms, of which form I is metastable at room temperature and form II is thermodynamically stable at room temperature.
If active compounds occur in different crystal forms (=polymorphism), this is of great importance both for designing preparation processes and for developing formulations. Thus, the different forms of a chemical compound differ, in addition to appearance (crystal habit) and hardeness, also in numerous further physicochemical properties. Here, differences in stability, solubility, hygroscopicity, melting point, particle density and flowability may exert a strong influence on the quality and the effectiveness of crop treatment agents. Hitherto, it has not been possible to predict the occurrence and the number of crystal forms including their physicochemical properties. In particular, the thermodynamic stability and also the different behaviour following administration to living organisms cannot be determined a priori.
It is generally known that the different forms of a substance can be monotropic or enantiotropic. In the case of monotropic polymorphism, a crystal form may represent the thermodynamically stable phase over the entire temperature range up to the melting point, whereas in the case of enantiotropic systems there is a transition point in which the stability relation is reversed. It is not possible to predict the stability relation, in particular the existence and the position of such a transition point. An up-to-date review of the prior art with respect to these principal thermodynamic relations is given in Angew. Chem. Int. Ed. 1999, 38, 3440–3461.